Abstract 1948: Tissue accumulation and release of platinum from a novel chitosan-hybrid gel after intraperitoneal drug delivery

Abstract

Abstract Gynecological malignancies such as cervical, endometrial and ovarian cancer still are the leading causes of death for women worldwide. However, standard therapies such as surgical cytoreduction and systemic chemotherapy combined with radiation have shown limited-efficacy by accessibility as well as nonspecific toxicity. To overcome those limitations, we previously reported about the development of a muco-adhesive, chitosan-hybrid gel (CS(BCDDP)) embedded with alginate beads containing cisplatin (CDDP) for a local, intraperitoneal application (# 3232, AACR 2011). Here we report the results of CDDP release from the (CS(BCDDP)), its cellular activity in vitro and CDDP accumulation to genomic DNA (gDNA) of tissues in vivo. To determine the amount of CDDP released from (CS(BCDDP)) in vitro, we used a colorimetric SnCl2 assay following the incubation in 0.9% NaCl solution for 24 hrs. (CS(BCDDP)) demonstrated successful release of 90% CDDP within 2 hrs and consistent CDDP-release could be maintained for up to 24 hrs. To test activity of CDDP released from (CS(BCDDP)), clonogenic assay was performed with Hela (human cervical adenocarcinoma) cells. Cells treated with (CS(BCDDP)) demonstrated a significantly low number of colonies, generating 9 (± 6) colonies per 500 cells seeded compared with 233 (± 10) colonies per 500 cells treated with an empty, no drug containing control gel (CS). To further assess CDDP accumulation to gDNA of tissues in vivo, inductively coupled plasma mass spectrometry (ICP-MS) was performed with tissue samples obtained from the left peritoneal sidewall of female nude mice following treatment with a control gel mixed with CDDP (CSCDDP), (CS(BCDDP)), and intravenously (i.v.) CDDP(CDDPIV). The results demonstrated a greater than three-time enhancement of CDDP-accumulation to the gDNA from (CS(BCDDP)) when compared to CDDPIV. Moreover, (CS(BCDDP)) also demonstrated higher accumulation of CDDP to gDNA when compared with CSCDDP. Relative values were 3.2 (±0.9) for (CS(BCDDP)) and 1.3 (± 0.4) for CSCDDP compared to values obtained from CDDPIV. Our in vitro and in vivo results, strongly suggest the feasibility of applying this hybrid gel locally to mucosal surfaces of the female reproductive tract and its advantage for intraperitoneal drug accumulation. Currently ongoing experiments are evaluating the efficacy and safety of our hybrid gel/CDDP in orthotopic endometrial, ovarian and cervical cancer animal models. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1948. doi:1538-7445.AM2012-1948